We propose to continue our investigation of the system responsible for the renal tubular reabsorption of filtered cadmium metallothionein (CdMT), and of its toxicological significance. CdMT has proven useful as model for the study of tubular proteinuria of the type seen in Cd poisoning. In particular it will be of interest to define further the substrate specificity of the saturable system previously shown to mediate the metallothionein reabsorption. Thus, myoglobin has so far proven to be the only (competitive?) inhibitor of this process. The use of hemoglobin instead of myoglobin should help decide whether the reabsorption is due to a system specific for low molecular weight proteins only. Critical in the process of protein reabsorption is the interaction between protein and brush border membrane. To help localize some of the steps in reabsorption the reaction of membrane vesicles with metallothionein and other proteins will be investigated. Such studies may help decide whether membrane reactions can explain the consistently observed tubular transit delay of CdMT.